Kalantar_edit.qxp 8/2/08 17:29 Page 39
The Ability of Albumin to Predict Outcome in Haemodialysis Patients
including albumin, is reduced.
37
Both CRP and cytokine levels predict
Figure 3: Outcomes According to Quartiles of Serum Albumin at
CVD in patients without renal disease as well as mortality from
Initiation of Haemodialysis
vascular disease.
38–40
Among patients with renal failure, those with
elevations in CRP or those with hypoalbuminuria also have significant
Number of admissions
A
increase in vascular disease
6
and increased risk of death from
2.5
cardiovascular causes.
29
Approximately 30% of HD patients have
2.0
increased levels of CRP,
6,29,41
consistent with the increased prevalence
of vascular disease in this population.
1
Detailed albumin kinetics
1.5
studies performed in a subset of Hemodialysis (HEMO) Study patients
1.0
concluded that a reduction in serum albumin in well-dialysed
patients was largely due to an increase in the level of inflammation
0.5
rather than a reduction in protein intake.
42
0.0
Highest quartile Lowest quartile
As well as having an effect on protein synthesis, inflammation is
Length of stay in hospital (days) B
14
associated with marked increases in resting energy expenditure and
12
albumin fractional catabolic rate.
23
Thus, two important mechanisms
10
that could protect albumin levels in HD patients are eliminated.
8
Therefore, it is likely that inflammation either has a direct effect
on albumin levels by suppressing albumin synthesis or increasing
6
the albumin fractional catabolic rate (FCR), or acts together
4
with malnutrition by potentiating the effect of protein
2
calorie malnutrition.
43 0
Highest quartile Lowest quartile
Hospital cost (US$) C
The relationship between albumin levels in HD patients and markers of
45,000
inflammation such as CRP and nutritional status was evaluated over a
40,000
35,000
three-month period in a group of 115 HD patients.
41
Serum albumin
30,000
levels were found to correlate negatively with CRP and serum amyloid
25,000
A levels (p<0.001), as well as with the protein catabolic rate (p<0.001) 20,000
(see Figure 2). Further sequential assessment of albumin and CRP
15,000
levels showed that, in the very short term, albumin concentration
10,000
5,000
varied with levels of CRP or the cytokine IL-6.
44
As levels of CRP
0
increased, albumin levels were reduced, but this effect was modulated
Highest quartile Lowest quartile
by the protein catabolic rate. Exploratory longitudinal studies later A: number of hospital admissions according to quartiles of serum albumin. Bars represent the
established that a decrease in albumin levels of more than 0.3g/dl
mean number of hospital admissions in days. B: length of hospital stay according to quartiles
of serum albumin: bars represent the mean length of stay in days. C: hospital costs according
for a period of more than six weeks was associated with a reduction
to quartiles of serum albumin. Bars represent the mean cost in US$.
Adapted from Pupim LB, et al.
53
in the rate of albumin synthesis and increased levels of acute-phase
proteins, with no reduction in the protein catabolic rate.
23
In malnourished dialysis patients with elevated CRP levels, carotid
intima-media thickness was significantly increased compared with
How Does Hypoalbuminuria Contribute to the High well-nourished HD patients with normal CRP levels.
6
These findings
Morbidity and Mortality Rate in Haemodialysis Patients? prompted the suggestion that inflammation and nutrition may be key
The prevalence of hypoalbuminuria increases as renal failure factors in the development of atherosclerosis.
6
As inflammation and
progresses. The primary cause of morbidity and mortality in HD patients nutrition are both associated with increased mortality in the HD patient
is atherosclerotic disease.
5,45
Additionally, congestive heart failure (CHF) population and are also both primary factors determining low serum
as a consequence of cardiomyopathy may reduce life expectancy in albumin concentrations, albumin may potentially be either a serological
these patients.
46,47
Factors such as an increased incidence of diabetes, marker of inflammation superimposed on malnutrition or contribute to
hypertension and hyperlipidaemia are likely to play a role in the accelerated mortality in this population.
increased prevalence of atherosclerotic disease in patients with ESRD.
However, data from Cheung and co-workers
48
suggest that traditional Healthcare Costs Associated with Hypoalbuminuria
risk factors alone do not account for the increased CVD mortality in In the US, total hospital admission rates for HD patients during 2005
ESRD patients, and that the influences of oxidative stress, endothelial were estimated to be 2,026 per 1,000 patient-years, with the average
dysfunction and chronic inflammation appear to be more important.
49
number of hospitalisation days estimated to be 14.3 per patient per
Accelerated atherosclerosis and CHF are associated with increased year.
2
Per person per year, treatment costs for HD patients averaged
levels of pro-inflammatory cytokines, such as CRP, as well as US$69,758.
2
Analysis of hospitalisation data from 1,846 HD patients
malnutrition. Pro-inflammatory cytokines are pivotal to the enrolled in the HEMO study showed that the likelihood of a severe
inflammation that is associated with malnutrition and atherosclerosis in outcome (death, intensive care unit stay or hospitalisation >7 days)
ESRD, while malnutrition appears to worsen patient outcome by significantly increased with decreased serum albumin levels
aggravating existing inflammation and heart failure, accelerating (p<0.001).
51
Of patients enrolled in the study, 783 (42.4%) had at
atherosclerosis and increasing susceptibility to infection.
50
least one infection-related hospitalisation and 58% of patients with a
EUROPEAN RENAL DISEASE 2007 39
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